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QUESTION: In patients with chronic asthma, are regular inhaled long acting β2 agonists (LABAs) more effective than regular inhaled short acting β2 agonists (SABAs)?
Studies were identified by searching the Cochrane Airways Group Trials Register and bibliographies of relevant articles and by contacting experts in the field.
Studies were selected if they were randomised controlled trials (RCTs) that lasted ≥2 weeks and compared a LABA with regular doses of any SABA in children and adults with chronic asthma (for ≥6 mo).
2 reviewers independently extracted data on patients; intervention; study design, setting, and quality; and outcomes. Main outcomes included daytime and nighttime asthma symptom scores, bronchodilator use for symptom relief, daily peak flow measurement, clinic measurements of airway function, quality of life score, asthma exacerbation rates, and adverse effects.
31 RCTs (24 parallel group and 7 crossover design) met the selection criteria. LABAs evaluated included salmeterol xinafoate (22 RCTs) and formoterol fumarate (9 RCTs). SABAs evaluated included salbutamol sulphate (26 RCTs) and terbutaline sulphate (5 RCTs). Only parallel group RCTs of adolescents or adults (>12 y of age) were included in meta-analyses using a fixed effects model. LABAs were better than SABAs for improving peak expiratory flow, forced expiratory volume in 1 second, forced vital capacity, symptom scores, rescue bronchodilator use, and quality of life (table).
In patients with chronic asthma, regular inhaled long acting β2 agonists are more effective than regular inhaled short acting β2 agonists.
The review by Walters et al nicely documented the advantages of LABAs over SABAs for short term application in asthma. This relative advantage is expected because of the longer duration of action of the LABAs. Not surprisingly, objective measures of airway calibre such as peak flow and forced expiratory volume in 1 second are better during any given 24 hour period, and symptom scores provoking need for rescue doses of β2 agonists are decreased. There seems to be no question that if a maintenance β2-agonist is used in asthma, then a LABA is superior to a SABA.
However, the review raises several important questions: Do these advantages continue long term? Do LABAs have an adverse effect on more severe exacerbations and asthma mortality? Are there better alternatives to β2 agonist add on therapy? In fact, do these medications really add to asthma’s ultimate outcome or do they merely improve snapshots of lung function? Are patients more prone to self treatment without medical supervision? Do patients using LABAs fail to be compliant with inhaled corticosteroid (ICS) therapy?
Besides looking at longer durations of therapy, future studies should also assess attrition with ICS adherence in patients taking LABAs because ICS should remain an underlying anti-inflammatory therapy, in line with current standards in asthma therapy.1 The 2 common LABAs, formoterol and salmeterol, should be compared for long term effects on tolerance, bronchial protection, and airway hyper-reactivity, which may predict the frequency and intensity of more severe exacerbations. These episodes often require escalation in corticosteroid therapy, emergency room visits, and hospital admissions. It’s these latter outcomes that contribute to the major morbidity and mortality of asthma and would readily warrant the cost of an additional medication. Finally, such multiple maintenance medications need to be compared with new strategies such as omalizumab recently approved in the US.2
For now, the review by Walters et al confirms that LABAs are superior to SABAs for the short term improvement of lung function and decrease in β2 agonist rescue doses, with formoterol having advantages over salmeterol. However, this addition should only be used as a second or third line maintenance treatment to be consistent with the current asthma guidelines. It should be applied only to those patients who receive symptomatic benefit, where cost is not prohibitive, and anti-inflammatory therapy is not compromised.
Source of funding: not stated.
For correspondence: Professor EH Walters, University of Tasmania, Hobart, Tasmania, Australia.
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